Know Cancer

forgot password

A Phase II Pharmacodynamic Investigation of the Efficacy of Vorinostat to Induce Fetal Hemoglobin in Adults With Severe Sickle Cell Disease Who Have Not Benefitted From Prior Therapy

Phase 2
18 Years
Open (Enrolling)
Sickle Cell Disease, Sickle Cell Anemia

Thank you

Trial Information

A Phase II Pharmacodynamic Investigation of the Efficacy of Vorinostat to Induce Fetal Hemoglobin in Adults With Severe Sickle Cell Disease Who Have Not Benefitted From Prior Therapy

- Since we are looking for the highest dose of vorinostat that can be administered safely
without severe or unmanageable side effects in participants who have SCD, the
participants dose may change while they are enrolled in the study.

- Participants will receive an initial dose of vorinostat for the first cycle (or 4
weeks). If they tolerate this dose, they will receive a higher dose for the second
cycle. The dose will be increased a 2nd time if they tolerate the dose of the second
cycle. Participants will continue on that highest dose for as long as they can
tolerate it, or, for a maximum of 4 cycles. The maximum dose participants could
receive is 400mg a day, 3 times a week.

- Participants will be given a study drug diary for each study cycle to record each time
they take vorinostat and indicate if they have any changes in their health or in
medications they are taking.

- During the study participants will come to the clinic for visits with the study team
and may have some of the following tests: physical examination, EKG, blood tests, urine
tests and echocardiogram.

Inclusion Criteria:

- Diagnosis of sickle cell disease

- Clinically significant disease defined as at least 1 painful episode per year
averaged over the previous 3 years or a history of priapism, stroke, acute chest
syndrome, avascular necrosis, multi-organ failure or the need for chronic narcotic
medications for pain from sickle cell disease

- Must have failed a previous attempt at treatment with hydroxyurea defined as the
inability to achieve a significant absolute increase in % fetal hemoglobin or the
inability to tolerate hydroxyurea treatment due to severe side effects such as but
not limited to myelosuppression, gastrointestinal symptoms, edema or hepatic enzyme
elevations or have contraindications to hydroxyurea

- 18 years of age or older

- Hematologic laboratory values as outlined in the protocol

- Non-hematologic laboratory values as outlined in the protocol

- Must agree not to donate blood or other bodily fluid while taking the study drug and
for 28 days thereafter

- Women of child-bearing potential (WCBP) must have a negative serum pregnancy test 72
hours or less prior to starting treatment

- Women of child-bearing potential and men must agree to use 2 forms of adequate
contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

- Subjects with hemoglobin SC or SB+ thalassemia

- Subjects on chronic transfusion program

- Subjects who have received RBC transfusions cannot have >15% adult hemoglobin

- Known positive status for HIV, active hepatitis B or hepatitis C

- Pregnant or breast feeding women

- Individuals with a history of malignancy are ineligible except for the following
circumstances. Individuals with a history of malignancy are eligible if they have
been disease-free for at least 5 years and are deemed by the investigator to be at
low risk for recurrence of that malignancy. Individuals with the following cancer
are eligible if diagnosed and adequately treated within the past 5 years: cervical or
breast cancer in situ, and basal cell or squamous cell carcinoma of the skin

- Subjects with a history of thrombosis or other reason (other than sickle cell
disease) for enhanced thrombotic risk

- Subjects with unresolved infections

- Severe or uncontrolled medical conditions that could compromise study participation

- Subjects on fetal hemoglobin inducing agents

- Subjects on any other experimental treatment within 90 days of the first dose of
study drug or who have not recovered from the side effects of such therapy

- Known allergic reaction to a histone deacetylase inhibitor

- Subjects who have received valproic acid for treatment of epilepsy within 30 days of

- Subjects who have received any HDAC inhibitors other than valproic acid

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the efficacy of vorinostat when administered orally in inducing a 4% absolute increase or a 100% increase in fetal hemoglobin levels in subjects with severe sickle cell disease who have failed prior therapy.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Maureen Okam, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Brigham and Women's Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

October 2009

Completion Date:

October 2014

Related Keywords:

  • Sickle Cell Disease
  • Sickle Cell Anemia
  • fetal hemoglobin
  • vorinostat
  • HDAC inhibitor
  • SAHA
  • Anemia
  • Anemia, Sickle Cell



Dana-Farber Cancer Institute Boston, Massachusetts  02115
Brigham and Women's Hospital Boston, Massachusetts  02115
Children's Hospital Boston Boston, Massachusetts  02115